Research objectives are to study the interrelationships of nutritional, metabolic and genetic factors as causative agents and modulators of obesity and the associated noninsulin dependent diabetes. The genetically obese mouse is the experimental animal model for this research with biochemical techniques applied at the whole animal, tissue and cellular levels. We propose to measure insulin sensitivity of soleus muscle prior to and shortly after weaning using insulin binding techniques and by measuring incorporation of 5- 3H-glucose into 3H-glycogen and 3H2O in order to establish when insensitivity of muscle to insulin first occurs in obese mice. The time of first occurrence of increased rates of fatty acid synthesis in various tissues from obese mice will be documented through in vivo incorporation of 3H2O into fatty foods. Other studies will measure fat cell development. These results will be used to establish the time-frame for development of the obese/ diabetic syndrome. In addition, both high fat and high carbohydrate diets will be fed duing gestation and the early developmental period of obesity in these animals to determine how nutrition can modulate the abnormal condittons of insulin insensitivity, increased lipogenesis and adipocyte hyperplasia in this syndrome.